Polyphyllin I, also known as Polyphyllin D and abbreviated as PPD or PPI, is 4-O-arabinofuranosyl-2-O-rhamnopyranosyl-β-D-glucopyranosyldioscin, a small molecular monomer extracted from the traditional Chinese medicine Paris Polyphylla also known as windpipe trachea. Paris Polyphylla has antibacterial, anti-inflammatory, analgesic, tranquilizing, and antitumor effects. Research has found that its main active component, Polyphyllin I, exerts its antitumor effects mainly by means of inducing apoptosis. Polyphyllin I has significant inhibitory effects on various tumor cells and is considered a natural medicine with good application prospect.
Studies have reported that the effects of Polyphyllin I on the radiosensitivity of nasopharyngeal carcinoma CNE-2 cell line are observed by using DDP as a positive control, said DDP having significant sensitizing effects on nasopharyngeal carcinoma. Results have shown that Polyphyllin I has time- and dose-dependent inhibitory effects on the proliferation of CNE-2 cells and has concentration-dependent radiosensitizing effects on the cell lines (HUA Yonghong et al., Effect of Polyphyllin I on Radiosensitivity in Nasopharyngeal Carcinoma Cell Line CNE-2 in vitro, Chinese Archives of Traditional Chinese Medicine, Vol. 29(6), 2011, pp. 1387).
XIAO Meifang et al. have discussed the in vitro effects of Polyphyllin I on the proliferation and apoptosis of human hepatocellular carcinoma SMMC-7721 cell line and related mechanisms. Studies have shown that Polyphyllin I can inhibit the proliferation of hepatocellular carcinoma SMMC-7721 cells in a time- and concentration-dependent manner. It is possible that Polyphyllin I inhibits the proliferation of the hepatocellular carcinoma cells via the mechanism of retarding the growth of the tumor cells and inducing cell apoptosis (XIAO Meifang et al., Growth and Apoptosis Effects of Paris Saponin I on Human Hepatocellular Carcinoma Cells, Life Science Research, Vol. 15(6), 2011, pp. 519).
It is discovered in the studies on Polyphyllin I that very few literatures has reported on modifying the free hydroxyl of Polyphyllin I. YU Biao et al have prepared several acylated dioscin compounds by taking advantage of the catalysis of lipase, which includes the double acylation of the 3′,5′- and 2′,5′-hydroxyl of the arabinosyl of Polyphyllin I. However, it is discovered in the in vitro screening tests on the antitumor bioactivity of the compounds obtained, the compounds obtained are evaluated as having null or weak activities (YU Biao et al., Acylated Derivative of Dioscin and Its Producing Process and Use, [P] CN 1322729A, 2001).
The present invention has modified Polyphyllin I by acylating its 5′-arabinofuranosyl. The resulting compound has increased antitumor activity by multiple times as compared with Polyphyllin I, which has never been reported to date in any literature in the world. Thus, compounds of this type are promising to be developed as antitumor medicines available clinically.